Unraveling the complex genetics of familial combined hyperlipidemia

Figures & data

Figure 1. Overview of the associatedUSF1 region in Finnish and Mexican familial combined hyperlipidemia (FCHL) families. The associated region was restricted by ∼70% (from 46 kb to 14 kb) using two different populations, the Finns and Mexicans 17,26. The rs numbers of the single nucleotide polymorphisms (SNPs) are as follows: f11rs1 (rs836), f11rs4 (hCV1459766), f11rs5 (rs4339888), usf1s1 (rs3737787), usf1s2 (rs2073658), usf1s8 (rs2516838).

Table I. Summary of the genetic studies on the USF1 gene, the first gene identified for familial combined hyperlipidemia (FCHL) using positional cloning approach.

Trait	Study sample	Marker/SNP	Positive (+)/negative (−) results	Reference
FCHL and/or TGs	Finnish FCHL families	rs836	+	17
		rs790056	+
		hCV1459766	+
		rs4339888	+
		rs3737787	+
		rs2073658	+
		rs2516839	+
		rs2516838	+
FCHL and/or TGs	Mexican FCHL families	rs3737787	+	26
		rs2073658	+
		hCV1459766	+
FCHL, TGs and/or LDL‐C	Utah families with premature CHD, stroke or hypertension	rs3737787	+	57
		rs2073658	+
LDL‐C and/or glucose	Caucasian males with family history of CHD and controls	rs3737787	+	56
		rs2073658	+
Cardiovascular event and/or all cause mortality (association with individual SNPs or 6‐SNP haplotype)	Finnish CHD cases and population‐based cohort	rs10908821	+	55
		rs2073658	+
		rs2774276	+
		rs2516839	+
		rs1556259	+
		rs2774279	+
Lipolytic activity in adipose tissue	Caucasian obese women	rs3737787	+	54
		rs2073658	+
T2DM and/or metabolic syndrome	Chinese T2DM families	rs3737787	+	58
		rs2516841	+
		rs2516839	+
T2DM and/or metabolic syndrome	Chinese cases and controls	rs3737787	−
		rs2516841	−
		rs2516839	−
T2DM	Cases and controls for T2DM	rs2516837	−	59
		rs1556259	−
		rs2516838	−
		rs2073653	−
		rs2774276	−
		rs2516841	−
		rs2073658	−
		rs3737787	−

CHD = coronary heart disease; LDL‐C = low‐density lipoprotein cholesterol; SNP = single nucleotide polymorphism; T2DM = type 2 diabetes mellitus; TG = triglycerides.

Table II. Genes associated with familial combined hyperlipidemia (FCHL) in previous studies.

Gene	Ethnicity	Replicated (at least once)	Reference
USF1	Finnish, Mexican and Caucasian (Utah) FCHL families	Yes	17, 26, 57
APOA1/C3/A4/A5	Caucasian (Dutch, Spanish, Northern European, European)	Yes	65–73, 88–90
LPL	Caucasian (Dutch and Italian)	Yes	96–105
HNF4A	Finnish and Mexican FCHL families	No (only one study)	18
CD36/FAT	Caucasian (Dutch)	No (only one study)	135
TNFRSF1B	Caucasian (Dutch)	No (only one study)	126
LEPR	Caucasian (Dutch)	No (only one study)	127

Figure 2. Multiple genetic and environmental factors confer the susceptibility to familial combined hyperlipidemia(FCHL).

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